San Diego—In hemodialysis patients in Japan, PA21 (sucroferric oxyhydroxide [SFOH]) was well tolerated in the long term and had a low pill burden. That was among the findings of an open-label, multicenter study conducted in Japan to assess the long-term safety and efficacy of SFOH following a 52-week treatment period.
Fumihiko Koiwa, MD, PhD, and colleagues presented results of the study during a poster session at Kidney Week 2015. The poster was titled Phase III Study to Investigate the Long-Term Efficacy, Safety, and Tolerability of PA21 (Sucroferric Oxyhydroxide) in Japanese Hemodialysis Patients with Hyperphosphatemia.
A previous in vitro study demonstrated that the phosphate binding capacity of SFOH was above a physiologically relevant pH range in the gastrointestinal tract. In the current study, doses of SFOH were titrated to maintain predefined concentrations of serum phosphorus of 3.5 to 6.0 mg/dL. Those were within the range recommended by the Japanese Society for Dialysis Therapy Chronic Kidney Disease-Mineral and Bone Disorder guideline.
Key inclusion criteria were age ≥20 years; undergoing maintenance hemodialysis three times a week for ≥12 weeks prior to the initiation of the screening period; and serum phosphorous concentration ≥3.5 mg/dL and ≤10.0 mg/dL with phosphate binders or >6.0 mg/dL and ≤10.0 mg/dL without phosphate binders. Key exclusion criteria included serum calcium concentration ≤7.5 mg/dL, or >11.0 mg/dL, at the beginning of the week in the screening period; intact-parathyroid hormone concentration >800 pg/mL at the beginning of the week at the initiation of the screening period; a history of hemochromatosis, or any other iron overload disorder, or serum ferritin >800 ng/mL, or transferrin saturation (TSAT) >50% at the beginning of the week in the screening period; and clinically significant gastrointestinal disorders based on the investigator’s diagnosis.
Of the 181 enrolled patients, 161 were administered the study drug. Of those, 45 discontinued treatment (24 due to an adverse event, four due to phosphorus decrease, four due to calcium decrease, two due to ferritin increase, and 14 due to other causes). Among the 260 patients in the full analysis set, mean age was 58.5 years, 70.6% were male, and mean dialysis vintage was 85.3 months.
Efficacy End Points
Mean serum phosphorous concentrations decreased from 5.46 mg/dL at week 0 to 5.00 mg/dL at the end of treatment; mean serum phosphorous concentrations were maintained within the target range of 3.5 to 6.0 mg/dL throughout the 52-week treatment period. Mean number of SFOH tablets was 3.3 pills/day; mean dose of SFOH was 1,141 mg/day.
Safety End Points
Overall, the incidence of adverse events was 94.4% and the incidence of adverse drug reactions was 32.3%. Diarrhea (22.4%) and constipation (2.5%) were frequently seen adverse drug reactions; there were no reports of severe diarrhea or constipation. Most of the adverse drug reactions were seen soon after initiation of SFOH and they did not increase in incidence over the long-term treatment.
There was a tendency for iron parameters, including serum ferritin, TSAT, and hemoglobin, to increase. Median serum ferritin levels increased from initiation of SFOH until week 24 and stabilized thereafter.
“These results suggest that SFOH is a promising drug for the long-term management of hyperphosphatemia in dialysis patients,” the researchers said.
Source: Koiwa F, Fukagawa M, Yokoyama K, Akizawa T. Phase III study to investigate the long-term efficacy, safety, and tolerability of PA21 (sucroferric oxyhydroxide) in Japanese hemodialysis patients with hyperphosphatemia. Abstract of a poster presented during American Society of Nephrology Kidney Week 2015, November 6, 2015, San Diego, California.